Muscle acylcarnitines during short-term fasting in lean healthy men.
The transition from the fed to the fasted resting state is characterized by, among other things, changes in lipid metabolism and peripheral insulin resistance. Acylcarnitines have been suggested to play a role in insulin resistance, as well as other long-chain fatty acid metabolites. Plasma levels of long-chain acylcarnitines increase during fasting, but this is unknown for muscle long-chain acylcarnitines. In the present study we investigated whether muscle long-chain acylcarnitines increase during fasting and we investigated their relationship with glucose/fat oxidation and insulin sensitivity in lean healthy humans. After 14 h and 62 h of fasting, glucose fluxes, substrate oxidation, and plasma and muscle acylcarnitines were measured before and during a hyperinsulinaemic-euglycaemic clamp. Hyperinsulinaemia decreased long-chain muscle acylcarnitines after 14 h of fasting, but not after 62 h of fasting. In both the basal state and during the clamp, glucose oxidation was lower and fatty acid oxidation was higher after 62 h compared with 14 h of fasting. Absolute changes in glucose and fatty acid oxidation in the basal compared with hyperinsulinaemic state were not different. Muscle long-chain acylcarnitines did not correlate with glucose oxidation, fatty acid oxidation or insulin-mediated peripheral glucose uptake. After 62 h of fasting, the suppression of muscle long-chain acylcarnitines by insulin was attenuated compared with 14 h of fasting. Muscle long-chain acylcarnitines do not unconditionally reflect fatty acid oxidation. The higher fatty acid oxidation during hyperinsulinaemia after 62 h compared with 14 h of fasting, although the absolute decrease in fatty acid oxidation was not different, suggests a different set point.
Soeters
Maarten R
MR
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands. m.r.soeters@amc.uva.nl
Sauerwein
Hans P
HP
Duran
Marinus
M
Wanders
Ronald J
RJ
Ackermans
Mariëtte T
MT
Fliers
Eric
E
Houten
Sander M
SM
Serlie
Mireille J
MJ
D000328:Adult; D000886:Anthropometry / Q000379:methods; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect / Q000379:methods; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D005215:Fasting / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D055815:Young Adult
D001786:Blood Glucose; C116917:acylcarnitine; D002331:Carnitine